A Phase I, Single-sequence, Open-label Study to Evaluate the Drug-Drug
Interaction Between Hetrombopag and Cyclosporine in Healthy Chinese
Subjects.
Abstract
Aims: This study aims to evaluate the drug-drug interaction(DDI)
between hetrombopag and cyclosporine in healthy Chinese subjects.
Methods: Twenty-six eligible subjects enrolled in this single-center,
single-sequence, open-label, DDI study with three treatment periods,
receiving 5 mg hetrombopag once on day 1, 100 mg cyclosporine twice
daily from day 11 to day 15, and 5 mg hetrombopag + 100 mg cyclosporine
on day 16. Serial blood samples were collected for pharmacokinetic
evaluation. Adverse events were monitored throughout the study. Results:
The plasma hetrombopag geometric mean ratios (GMRs) (90% CI) of Cmax,
AUC0-t and AUC0-∞ of co-administration of hetrombopag with cyclosporine
vs hetrombopag alone are 95.97% (70.08%, 131.43%), 105.75% (75.04%,
149.04%) and 104.19% (74.71%, 145.32%), respectively, indicating
multiple doses of cyclosporine had minimal effects on hetrombopag
exposure. The GMRs (90% CI) of Cmax and AUCss,tau for blood
cyclosporine of co-administration vs cyclosporine alone were 100.49%
(91.89%, 109.89%) and 100.81% (107.88%, 103.82%), respectively,
suggesting a single dose of hetormbopag had no impact on the exposure of
cyclosporine. Co-administration of hetormbopag with cyclosporine was
generally well tolerated. Conclusion: No clinically significant DDI was
observed when co-administration of hetrombopag with cyclosporine. No
additional dose adjustment is warranted for this combination.